(a) Field of the Invention
This invention relates to 3-arylcarbonyl-1-(C-attached-N-heteryl)-1H-indoles which are useful as analgesic, antirheumatic, anti-inflammatory and antiglaucoma agents.
(b) Information Disclosure Statement
It is believed that compounds of the indole series having a nitrogen-containing heterocyclic group attached to the nitrogen atom of the indole either directly through a carbon atom of the heterocycle or through an intervening alkylene group attached to a carbon atom of the heterocycle and having, in addition, any carbonyl-containing function at the 3-position of the indole nucleus are unknown.
3-Arylcarbonyl substituted-1H-indoles having a nitrogen-containing heterocyclic group attached to the 1-position through the nitrogen atom of the heterocycle have been disclosed in the prior art, for example in Deschamps et al. U.S. Pat. No. 3,946,029, which describes compounds useful as fibrinolytic and anti-inflammatory agents, and in Bell U.S. Pat. No. 4,634,776, which discloses compounds useful as analgesic, antirheumatic and anti-inflammatory agents.
Essentially the same disclosure of Deschamps U.S. Pat. No. 3,946,029 is found in Inion et al., Europ. J. of Med. Chem., 10(3), 276-285 (1975). Specifically disclosed in both the Deschamps and Inion et al. references is 2-isopropyl-3-(3-pyridylcarbonyl)-1-[2-(4-morpholinyl)ethyl]indole.
Herbst U.S. Pat. No. 3,489,770 generically discloses compounds having the formula: ##STR1## where, inter alia, R.sub.1 is "diloweralkylamino, pyrrolidinyl, piperidino and morpholino and R.sub.2 is . . . cyclo (lower) alkanoyl and adamantanyl carbonyl". Although not within the ambit of the above-defined genus, the Herbst patent also discloses a variety of species where R.sub.2 is an arylcarbonyl group. Specifically disclosed, for example, is the species "1-p-(chlorobenzoyl)-3-(2-morpholinoethyl)indole". The compounds are said to possess anti-inflammatory, hypotensive, hypoglycemic and CNS activities.
Tambute, Acad. Sci. Comp. Rend., Ser. C, 278(20), 1239-1242 (1974) discloses compounds of the formula: ##STR2## where n is 2 or 3. No utility for the compounds is given.
1-Primary amino-lower-alkyl-3-arylcarbonyl-1H-indoles for which no utility is stated are disclosed by Dalla Croce, Chem. Abst., 80, 95655f (1974).
The prior art also discloses a number of indoles having no substituent at the 3-position and a C-attached heterocyclic alkyl group attached to the 1-position. For example Bosch et al., J. Org. Chem., 48(25), 4836-41 (1983) disclose the species 1-[(1-methyl-4-piperidinyl)methyl]-1H-indole; Bosch et al., Tetrahedron, 40(8), 1419-24 (1984) disclose 1-[(1-methyl-2-oxo-4-piperidyl)methyl]-1-indole and 1-](1-methyl-1,2,5,6-tetrahydro-4-pyridyl)methyl]-1H-indole; and Bennasar et al., Tetrahedron, 42(2), 637-647 (1986) disclose 1-[4-(3-methoxy-1-methyl-1,2,5,6-tetrahydropyridyl)-methyl]-1H-indole and 1-[4-(1-methyl-3-oxopiperidyl)methyl]-1H-indole, all useful as intermediates for the preparation of a partial structure of the indole alkaloid vinoxine.
Vartangan et al., Ann. Khim. Zh., 38(5), 308-313 (1985); Chem. Abst. 105, 114874e (1985) disclose compounds of the formula: ##STR3## where R is hydrogen, COOH or COOCH.sub.3, for which no utility is disclosed; Nilsson et al., Acta. Chem. Scand , Ser. B, B39(7), 531-537 (1985) disclose compounds having the formula: ##STR4## where X is 0 or S and R is hydrogen or methyl which were prepared for circular dichroism studies; and Sasakura et al., Syn. Comm. 18(3), 265-273 (1988) disclose compounds having the formula: ##STR5## where X is hydrogen, chlorine, fluorine or methoxy; Y is hydrogen or fluorine; R is methyl or benzyl and n is 1 or 2 for which no utility is disclosed.